The concentrations of cefamandole, cloxaciDin and fusicid acid were measured in the serum and heart tissue of 100 recipients of these drugs before cardiac surgery. During cardiopulmonary bypass, mean (± standard deviation) peak concentrations in serum of all patients were 63.0 ± 34.0 Lg of cefamandole per ml, 30.8 17.7 ,ug of cloxacillin per ml, and 32.4 ± 10.8 Fg of fusidic acid per ml. Mean (± standard deviation) concentrations in atrial appendages taken 1 h (±15 mi) after infusion were 21.3 ±11.0 ,ug of cefamandole per g, 23.8 ± 17.3 ,ug of cloxaciDin per g, and 10.7 ± 4.2 ,ug of fusidic acid per g. No cloxacillin coild be detected in 5 of 39 heart specimens. Mean tissue-to-serum ratios at 1 h for cefamandole, cloxacillin, and fusidic acid were respectively 0.35, 0.73, and 0.33. Fusidic acid, a drug which is highly effective in vitro against both methicillin-resistant Staphylococcus aureus and .taphylococcus epidermidis, was detectable in heart tissue in concentrations which were 12 times higher than the MICs of this agent against these resistant microorganisms.There are several published reports on the penetration of cefamandole in human heart but none on either cloxacillin, a drug which in several countries of the world is used as a prophylactic agent in cardiac surgery (3, 9), or fusidic acid, an agent of some promise because of activity in vitro against both methicillin-resistant and -susceptible Staphylococcus aureus and Staphylococcus epidermidis (4,20). The increasing incidence of severe infection due to those latter microorganisms (9,12,15) has stimulated us to compare the penetration of these three antibiotics in human heart.
MATERIALS AND METHODSPatients. A total of 100 patients (69 males and 31 females) about to undergo cardiac surgery were admitted into this study. They ranged in age from 21 to 84 years old (mean, 55 years). Men constituted 65% and 55% of the cefamandoleand cloxacillin-treated groups, respectively. They accounted for 90o of the fusidic acid group. Surgeries consisted of coronory bypass (CPB) (66%) and valve replacement (32%) for the cefamandole and cloxacillin groups and CPB for the fusidic acid group. Duration of surgery varied from 3 to 5 h. Extracorporeal circulation lasted 1 to 3 h. Drug administration. Cefamandole (Eli Lilly, Canada) was administered to 37 patients, and cloxacillin (Ayerst, Canada) was administered to 34 patients. At induction of anesthesia, both drugs were infused intravenously (i.v.) at a dose of 1 g over 5 min. Fusidate diethanolamine (Leo Laboratories, Canada) was administered to 29 patients i.v. at a dose of 580 mg over 2 h before surgery. After the first dose, cefamandole and cloxacillin were continued every 4 h for 24 h, and fusidic acid was continued every 8 h. Each patient received a total of six injections of either drug.Sample collection. Blood samples were collected 1, 2, 3, and 4 h after administration of either cefamandole, cloxacillin, or fusidate diethanolamine. Additional samples were collected at 5, 6, and 8 h from patients receiving fusi...